Council of State and Territorial Epidemiologists/CDC Surveillance Case Definition for Multisystem Inflammatory Syndrome in Children Associated with SARS-CoV-2 Infection — United States
Authors: Michael Melgar, Ellen H. Lee, Allison D. Miller, Sarah Lim, Catherine M. Brown, Anna R. Yousaf, Laura D. Zambrano, Ermias D. Belay, Shana Godfred-Cato, Joseph Y. Abrams, Matthew E. Oster, Angela P. Campbell
Journal: MMWR Recommendations and Reports (2022)

Since May 14, 2020, CDC has conducted national surveillance for multisystem inflammatory syndrome in children (MIS-C) associated with infection with SARS-CoV-2, the virus that causes COVID-19, among persons aged <21 years using a CDC case definition based on public health need and data from early reports of patients with this condition.Recent analyses of accumulated data indicated that certain criteria from the 2020 CDC MIS-C case definition performed better than others in distinguishing MIS-C from other illnesses and that certain other criteria likely contributed to misclassification.To incorporate lessons learned from MIS-C surveillance and public health investigations and to improve feasibility of implementation by surveillance staff at state, local, territorial, and tribal health departments, the Council of State and Territorial Epidemiologists (CSTE) and CDC developed a CSTE/CDC position statement (approved by CSTE in 2022) that includes an MIS-C surveillance case definition for voluntary reporting to CDC (effective January 1, 2023).This report summarizes the evidence and rationale supporting the components of the CSTE/CDC MIS-C surveillance case definition and describes the methods used to develop the definition.These methods included convening MIS-C clinical experts (i.e., consultants) regarding identification of MIS-C and its distinction from other pediatric conditions, a review of available literature comparing MIS-C phenotype with that of pediatric COVID-19 and other hyperinflammatory syndromes, and retrospective application of different criteria to data from MIS-C cases previously reported to CDC.The CSTE/CDC surveillance case definition for MIS-C includes four important changes, in comparison with the 2020 CDC MIS-C case definition.These changes are 1) no required duration of subjective or measured fever; 2) requirement of C-reactive protein ≥3.0 mg/dL to indicate systemic inflammation; 3) adjustments to criteria of organ system involvement to include addition of shock as a separate category and elimination of respiratory, neurologic, and renal criteria; and 4) new requirements on timing of positive SARS-CoV-2 laboratory testing relative to the MIS-C illness.Although MIS-C is not a nationally notifiable condition and reporting is voluntary, CSTE and CDC recommend that all states and territories report all cases meeting confirmed, probable, or suspect criteria of the CSTE/CDC MIS-C surveillance case definition beginning January 1, 2023, for cases with MIS-C illness onset on or after that date.MMWR / December 16, 2022 / Vol.71 / No. 4 US Department of Health and Human Services/Centers for Disease Control and Prevention of Paediatrics and Child Health in the United Kingdom also developed MIS-C case definitions for surveillance or clinical guidance, based on early clinical data.These definitions differed with respect to patient age limits, fever duration, and organ system involvement (13-15) (Supplementary Table 1, https://stacks.cdc.gov/view/cdc/121710).Development of an MIS-C case definition for national surveillance is challenging because of a lack of a confirmatory diagnostic laboratory test or pathognomonic clinical features that distinguish MIS-C from COVID-19 or other pediatric hyperinflammatory syndromes such as Kawasaki disease.As a result, the 2020 CDC MIS-C case definition is complex, relying on combinations of clinical features and supporting laboratory tests to establish inclusion criteria.However, review of the 2020 CDC MISC case definition identified areas where criteria could be simplified by clarifying the minimum required fever duration, reducing open-ended lists of organ-specific clinical criteria to a limited list of the most important MIS-C features, and narrowing the laboratory tests used as evidence of systemic inflammation.An additional consideration was to reduce misclassification.Recent analyses, including from the Overcoming COVID-19 Network MIS-C registry, a CDC-funded pediatric hospital surveillance network registry of MIS-C patients, have indicated that certain criteria from the 2020 CDC MIS-C case definition performed better than others in distinguishing MIS-C from other conditions (16,17).A joint CSTE/CDC work group* was established to develop a CSTE position statement for a standardized MIS-C surveillance case definition with reduced risk for misclassification and reduced complexity for better ease of implementation.The position statement was approved at the CSTE Annual Conference on June 23, 2022 (18).The purpose of this report is to describe the process and considerations that contributed to components of the CSTE/CDC MIS-C surveillance case definition and to encourage health departments to report all cases meeting confirmed, probable, or suspect criteria to CDC.